MXPA97006797A - Process for the preparation of acidoestilbendicarboxil esters - Google Patents

Abstract

The present invention relates to a process for the preparation of a dialkyl 4,4'-stilbenedicarboxylate having the formula: in the steps characterized in that they comprise: i) preparing the p (chloromethyl) benzoic acid by chlorinating the p-toluic acid with chloride of sulfuryl in the presence of a free radical initiator and chlorobenzene or dichlorobenzene, ii) contacting the p- (chloromethyl) benzoic acid of step (1) with a trialkyl phosphite having the formula (R2O) 3P to obtain a phosphonate compound having the formula: II and iii) contacting the phosphonate ester compound of step (2) with an alkyl p-formylbenzoate in the presence of an alkali metal alkoxide and an inert solvent to obtain the 4,4'-stilbenedicarboxylate of dialkyl, wherein R1 is alkyl of 1 to 6 carbon atoms and R2 is alkyl of 2 to 6 carbon atoms

Description

PROCESS FOR THE PREPARATION OF ESTERS OF ESTILBENDICARBOXILICO ACID DESCRIPTION OF THE INVENTION This invention relates to a novel process for the preparation of 4,4'-stilbenedicarboxylic acid esters. More specifically, this invention relates to a 3-step process for the synthesis of dialkyl esters of 4,4'-stilbenedicarboxylic acid from p-toluic acid and alkyl p-formylbenzoates using intermediates of the phosphite and phosphonate compounds. The 4, 4'-dialkyl styrylcarboxylates and 4,4'-stilbenedicarboxylic acid are used in the manufacture of brighteners or optical brighteners. For example, U.S. Patent 4,921,964 describes the preparation of the bis (2-benzoxazolyl) stilbene compounds by the reaction of the dialkyl stybenedicarboxylate esters with various 2-aminophenol compounds in the presence of certain solvents and catalysts. The optical brighteners are widely used in plastics and synthetic fibers to improve the appearance, for example, the apparent whiteness, of the same. The preparation of a mixture of 4,4 '-bibenzyldicarboxylic acid and 4,4'-stilbenedicarboxylic acid by heating a stoichiometric excess of p-toluic acid with sulfur is described in U.S. Patent 2,677,703. The disadvantages involved in this method for producing 4,4'-stilbenedicarboxylic acid include (1) elevated temperatures in the range of 250 to 290 ° C are required, (ii) the mixture of the product containing the initial material, the acid p -tolical and the 2 acid products 4, 4 '-bibenzyldicarboxylic acid and 4,4'-stilbendicarboxylic acid, are very difficult to separate, (iii) the low yields are obtained, for example, 40% is the best, and (iv) the need to avoid the hydrogen sulfide produced from the exhaust by expensive purification procedures. It is also known to heat a stoichiometric excess of p-toluic acid with sulfur at 265 ° C at a pressure of about 5.5 bar absolute in the presence of nitrogen to obtain 4,4'-stilbenedicarboxylic acid in a yield of 34% based on the amount of sulfur used A known method for synthesizing 4,4'-dimethyl dimethyl carboxylate comprises the steps of (1) contacting methyl p-formylbenzoate with hydrogen sulfide at 0 ° C in the presence of hydrochloric acid to produce a cyclic trisulfide compound and (2) to heat the cyclic trisulfide compound from 220 to 260 ° C in the presence of copper and diphenylether.The 4,4'-dimethyl dimethylcarboxylate is obtained in a total yield, based on the material initial of methyl p-formylbenzoate of 37.5% Both of these methods, such as the process of US Pat. No. 2,677,703, produce hydrogen sulphide, thus, require special equipment for treatment. the effluent of the process. These processes require the use of special, dedicated equipment and are not suitable for use in general purpose equipment. Additional methods are described for preparing stilbene compounds by K. B. Becker, Synthesis of Stilbenes, Synthesis, Major 1983, 341-368 and U.S. Patent 5,113,010. A new process has been developed which does not require the use of sulfur and can be operated under moderate conditions of the process in general purpose equipment, which manufactures chemicals. The process of the present invention provides a novel method for producing a 4,4'-styrylcarboxylic acid dialkyl ester having the formula by the steps comprising: (1) preparing the p- (chloromethyl) benzoic acid by chlorinating the p-toluic acid with sulfuryl chloride in the presence of a free radical initiator and chlorobenzene or dichlorobenzene; (2) contacting the p- (chloromethyl) benzoic acid of step (1) with a trialkyl phosphite having the formula (R20) 3P to obtain a phosphonate compound having the formula: and (3) contacting the phosphonate ester compound of step (2) with an alkyl p-formylbenzoate in the presence of an alkali metal alkoxide and an inert solvent to obtain dialkyl 4,4'-styrylcarboxylate; wherein R1 is alkyl of 1 to 6 carbon atoms and R2 is alkyl of 2 to 6 carbon atoms. The 3-stage process can be operated in general-purpose equipment in which steps (2) and (3) can be carried out in the same reactor. The first stage of the process is carried out in the chlorination equipment, in which the p-toluic acid is contacted with sulfuryl chloride in the presence of a free radical initiator and - chlorobenzene and / or dichlorobenzene to convert the p-toluic acid to p- (chloromethyl) benzoic acid or (a-chlorotoluic acid). This chlorination process is carried out at a temperature of 70 to 100 ° C at ambient or autogenous pressure using at least 1, and preferably 1.1 to 2 moles of sulfuryl chloride per mole of p-toluic acid. The free radical initiator can be selected from various peroxides such as aroyl peroxides, for example, benzoyl peroxide and azo compounds such as 2,2'-azobisisobutyr-nitrile and 1,1-azobis (cyclohexanecarbonitrile). The amount of the free radical initiator typically employed is in the range of 0.01 to 0.10 moles of initiator per mole of p-toluic acid. The use of chlorobenzene, dichlorobenzene or a mixture thereof as the process solvent produces an unexpected benefit in that the desired product, p- (chloromethyl) benzoic acid, is essentially insoluble in chlorobenzene and dichlorobenzene. In this way, p- (chloromethyl) benzoic acid, as formed during the chlorination step, precipitates and decreases the formation of the dichlorinated material, p- (dichloromethyl) -benzoic acid. Accordingly, step (1) of the process defined in the foregoing constitutes a separate embodiment of the present invention. The weight ratio of the chlorobenzene and / or dichlorobenzene solvent used for the initial p-toluic acid material is usually from 1: 1 to 5: 1, preferably from 2: 1 to 4: 1. The p- (chloromethyl) benzoic acid obtained in step (1) is isolated by filtration, usually washed to remove the residual sulphuryl chloride and initiator and used in step (2) without further purification.

Step (2) is carried out by simply heating a mixture of the p- (chloromethyl) benzoic acid of step (1) and a trialkyl phosphite at a temperature of 140 to 180 ° C. Step (2) is conveniently carried out using an excess of the trialkyl phosphite as the reaction solvent or medium. For example, the molar ratio of the trialkyl phosphite to the p- (chloromethyl) benzoic acid may be in the range of 2: 1 to 10: 1, preferably in the range of 3: 1 to 5: 1. Upon completion of step (2), the excess trialkyl phosphite (unreacted) is usually removed from the product by distillation. During the course of the reaction of step (2), the carboxyl group of the toluic acid is esterified with an alkyl group derived from the phosphite ester (R20) 3P. This esterification 'inherent in step (2) results in the formation of a stybenedicarboxylic acid diester more than a monoester. The third step of the process of the present invention comprises contacting the phosphonate ester compound of step (2) with an alkyl p-formylbenzoate having the structure R1-O? -. ^ "V-CHO (III) in the presence of an alkali metal alkoxide and an inert solvent to obtain dialkyl 4,4'-styryl-dicarboxylate. Examples of the alkali metal alkoxides which may be used in step (3) include the alkoxides of sodium, potassium, lithium and cesium containing from 1 to 4 carbon atoms. The amount of alkali metal alkoxide used is typically at least one mole of alkali metal alkoxide per mole of alkyl p-formylbenzoate, preferably 1.2 to 2.0 moles of alkali metal hydroxide per mole of alkyl p-formylbenzoate. Step (3) is typically carried out at a temperature of 25 to 35 ° C in the presence of an inert solvent, polar, aprotic. Inert solvents which may be used include dimethylformamide, dimethylacetamide, dimethyl sulfoxide, glycol diethers, glycol diesters, glycol ether esters and haloaromatics. With reference to step (1), the chlorination of toluene using sulfuryl chloride and benzoyl peroxide is described in Kharasch et al., J. Amer. Che. Soc. , 61, 2442 (1939). However, Case, J. Am. Chem. Soc. , 47, 3003 (1925) teaches the preparation of p- (chloromethyl) -benzoic acid by heating the p-cyanobenzyl chloride with concentrated hydrochloric acid for 10 hours. With reference to steps (2) and (3) the reaction of (i) a-bromotoluic acid and triethyl phosphite to produce diethyl p-carboxybenzylphosphonate and (ii) diethyl p-carboxybenzylphosphonate with p- (2-benzoxazolyl) benzaldehyde in the presence of DMSO and sodium methoxide to produce 4- (2'-benzoxazolyl) -4'-stilbenecarboxylic acid is described in Example 22 of U.S. Patent 3,586,673. Seus et al., Journal of Organic Chemistry, 26, 5243 (1961) describes the preparation of stilbene and heterocyclic analogues by heating a mixture of diethyl benzylphosphonate, benzaldehyde or a heterocyclic carboxaldehyde, sodium methoxide and dimethylfor amide. The novelty and inventive merit of the present process is mainly predicted in the unique combination of the stages, which require a minimum use of the general purpose equipment to operate on a commercial scale. For example, steps (2) and (3) may conveniently and economically be carried out in the same reaction vessel. The process of the present invention is further illustrated by the following examples. STAGE (1) A solution of p-toluic acid (27.2 g, 0.2 mol) in chlorobenzene is heated to 90 ° C in a 250 ml 3-necked flask, equipped with 2 drip funnels for the addition of the initiator and the chloride of sulfuryl. A solution of 1,1-azobis (cyclohexanecarbonitrile) (0.75 g) in 25 ml of chlorobenzene and sulfuryl chloride (48.7 g, 29 ml, 0.35 mol) are added simultaneously over a period of 30 minutes while a stream of sulfur dioxide gaseous and 'hydrochloric acid is generated and passed quickly in an alkaline solution. The mixture is heated at 90 ° C for 4 hours and any low-boiling compound formed is removed by distillation. The mixture is cooled to 15 ° C with a water-ice bath and the product, p- (chloromethyl) benzoic acid, is collected by filtration, washed with cold toluene (15 ° C) (4 x 25 ml) and It is dried in a vacuum oven at 60 ° C. The yield of the product is 26.0 g (76% theory) which has a purity of 95% as determined by gas chromatography. STAGE (2) A mixture of p- (chloromethyl) benzoic acid (24.0 g, 0.14 mol) and triethyl phosphite (95 g, 98 ml, 0.56 mol) is heated to 170 ° C (base temperature) for 6 hours in a 3-neck flask 250 ml. Excess triethyl phosphite and by-products are extracted by distillation under reduced pressure (approximately 150 torr) and less than 100 ° C (base temperature) for a period of about 1 hour. The reaction mixture is then cooled, toluene (100 ml) is added and the toluene solution of the product is washed with water (6 x 100 ml) at a pH of 4 to 5. The toluene is distilled off under reduced pressure ( 150 torr) and a temperature of less than 100 ° C (base temperature) for a period of approximately 1 hour. The product, consisting mainly of p- (ethoxycarbonyl) -benzylphosphonate diethyl, is obtained in a yield of 37 g (88% theory) and is used in step (3) without further purification. STAGE (3) A suspension of sodium methoxide (10.4 g, 0.19 mol) in dimethylformamide (DMF, 150 ml) is added slowly over a period of 15 to 20 minutes to a mixture of the phosphonate (37 g, 0.123 mol) of the step (2) and methyl p-formylbenzoate (20.2 g, 0.123 mol) in 100 ml of DMF while maintaining the mixture at 25 to 35 ° C by cooling with cold water. The stirring of the mixture is continued at 25 ° C for 4 hours. Water (200 ml) is slowly added while maintaining the temperature of 25 to 30 ° C and then stirring at 25 to 30 ° C is continued for 1 hour. The product is collected by filtration, it is washed with water (5 x 100 ml) at a pH of 6-7, washed with methanol and then dried. The yield of the product is 29.5 g, 80% theory. The FDMS analysis shows that a greater portion of the product is methyl ethyl diester and a minor portion is the dimethyl diester of 4, 4-styrynedicarboxylic acid.

Claims (9)

CLAIMS 1. A process.- for the preparation of a 4,4 'dialkyl stinbendicarboxylate that has the formula by the steps characterized in that they comprise: (i) preparing the p- (chloromethyl) benzoic acid by chlorinating the p-toluic acid with sulfuryl chloride in the presence of a free radial initiator and chlorobenzene or dichlorobenzene; (ii) contacting the p- (chloromethyl) benzoic acid of step (1) with a trialkyl phosphite having the formula (R20) 3P to obtain a phosphonate compound having the formula: R2-OC ~ / -CH. -I (OR2) (II) and (iii) contacting the phosphonate ester compound of step (2) with an alkyl p-formylbenzoate in the presence of an alkali metal alkoxide and an inert solvent to obtain dialkyl 4,4'-styrylcarboxylate; wherein R1 is alkyl of 1 to 6 carbon atoms and R2 is alkyl of 2 to 6 carbon atoms. 2. The process in accordance with the claim 1, characterized in that step (i) is carried out at a temperature of 70 to 100 ° C using 1.1 to 2 moles of sulfuryl chloride per mole of toluic acid, a free radical initiator selected from aroyl peroxides and azo compounds, and a solvent selected from chlorobenzene, dichlorobenzene or a mixture thereof in a weight ratio of the solvent: p-toluic acid in the range of 1: 1 to 5: 1. 3. The process in accordance with the claim 2, characterized in that the step (2) is carried out at a temperature of 140 to 180 ° C using an amount of trialkyl phosphite which gives a molar ratio of trialkyl phosphite to the p- (chloromethyl) benzoic acid of 2. : 1 to 10: 1. 4. The process in accordance with the claim 3, characterized in that step (3) comprises using 1.2 to 2.0 moles of alkali metal alkoxide per mole of alkyl p-formylbenzoate, a temperature of 25 to 35 ° C and an inert, polar, aprotic solvent. 5. The process according to claim 2, characterized in that: the step (2) is carried out at a temperature of 140 to 180 ° C using triethyl phosphite in which the mol ratio of the triethyl phosphite with the acid p- (chloromethyl) benzoic is in the range of 2: 1 to 10: 1; step (3) is carried out at a temperature of 25 to 35 ° C in the presence of an alkali metal alkoxide using 1.2 to 2.0 moles of alkali metal alkoxide per mole of methyl p-formylbenzoate and an inert, polar solvent , aprotic to obtain the 4, 4'-dialkyl styrylcarboxylate; and R1 is methyl and R2 is methyl or ethyl. The process according to claim 5, characterized in that the free radical initiator used in step (1) is selected from benzoyl peroxide, 2,2'-azobisisobutyrenitrile and 1,1-azobis (cyclohexane-carbonitrile); the molar ratio of the triethyl phosphite to the p- (chloromethyl) benzoic acid is in the range of 3: 1 to 5: 1; the alkali metal alkoxide used in step (3) is selected from the sodium and potassium alkoxides containing from 1 to 4 carbon atoms; and the inert, polar, aprotic solvent used in step (3) is dimethylformamide. 7. A process for the preparation of p- (chloromethyl) benzoic acid characterized in that it comprises chlorinating the p-toluic acid with sulfuryl chloride in the presence of a free radical initiator and in a solvent comprising chlorobenzene, dichlorobenzene or a mixture thereof. same. 8. The process according to claim 7, characterized in that the process is carried out at a temperature of 70 to 100 ° C using 1.1 to 2 moles of sulphuryl chloride per mole of toluic acid, a selected free radical initiator. of aroyl peroxides and azo compounds, and a solvent selected from chlorobenzene, dichlorobenzene or a mixture thereof in a weight ratio of the solvent p-toluic acid in the range of 1: 1 to 5: 1. 9. The process according to claim 8, characterized in that the free radical initiator is selected from benzoyl peroxide, 2,2'-azobisisobutyrenitrile and 1,1-azobis (cyclohexanecarbonitrile) and the weight ratio of the solvent: -toluico is in the range of 2: 1 to 4:

1.